MAC inhibitors suppress mitochondrial apoptosis

Pablo M. Peixoto, Shin Young Ryu, Agnes Bombrun, Bruno Antonsson, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

MAC (mitochondrial apoptosis-induced channel) forms in the mitochondrial outer membrane and unleashes cytochrome c to orchestrate the execution of the cell. MAC opening is the commitment step of intrinsic apoptosis. Hence closure of MAC may prevent apoptosis. Compounds that blocked the release of fluorescein from liposomes by recombinant Bax were tested for their ability to directly close MAC and suppress apoptosis in FL5.12 cells. Low doses of these compounds (IC50 values ranged from 19 to 966 nM) irreversibly closed MAC. These compounds also blocked cytochrome c release and halted the onset of apoptotic markers normally induced by IL-3 (interleukin-3) deprivation or staurosporine. Our results reveal the tight link among MAC activity, cytochrome c release and apoptotic death, and indicate thismitochondrial channel is a promising therapeutic target.

Original languageEnglish (US)
Pages (from-to)381-387
Number of pages7
JournalBiochemical Journal
Volume423
Issue number3
DOIs
StatePublished - Nov 1 2009

Keywords

  • Apoptosis
  • Cytochrome c release
  • Interleukin-3
  • Mitochondrial apoptosis-induced channel (MAC)
  • Patch-clamp
  • Staurosporine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Peixoto, P. M., Ryu, S. Y., Bombrun, A., Antonsson, B., & Kinnally, K. W. (2009). MAC inhibitors suppress mitochondrial apoptosis. Biochemical Journal, 423(3), 381-387. https://doi.org/10.1042/BJ20090664